The murine H-2 transplantation alloantigens are cell membrane integrated glycoproteins carrying the antigenic determinants involved in tissue graft rejection. The molecular expression of these antigens is controlled by an unusually complex and polymorphic genetic region in the IX linkage group. The long term objective of the proposed research project is to describe the molecular architecture of these membrane specific polymorphic gene products in order to understand the organization and expression of the H-2 genes as well as the structural and functional properties associated with the antigens themselves, as integral components of the plasma membrane. Specifically, we will study the H-2 gene products as isolated by the non-ionic detergent NP-40. This method is of particular significance since it offers high efficiency (80%), sensitivity, and specificity. Attention will center on understanding the nature of the H-2 antigenic sites by attempts to selectively modify them, and by attempts to isolate small fragments with antigenic activity. Comparative peptide analysis of antigen from selected strains of differing H-2 genotype will help pinpoint relevant peptides possibly responsible for observed antigenic differences, and with partial sequence analysis will help further to answer questions on antigenic site structure and on evolutionary properties of the H-2 genes. BIBLIOGRAPHIC REFERENCES: Nathenson, S.G. Cell membrane antigens determined by the mouse major histocompatibility complex - some data and some speculations. In Perspectives in Membrane Biology, First Mexican Society of Biochemistry Symposium, Eds., S. Estrada-O and C. Gitler, Academic Press, Inc., New York, p. 559, 1974. Cullen, S.E., Freed, J.H., Atkinson, P.H. and Nathenson, S.G. Evidence that protein determines Ia antigenic specificity. Transpl. Proc. VII, Suppl. 1, 237, 1975. Sachs, D.H., David, C.S., Shreffler, D.C., Nathenson, S.G. and McDevitt, H.O. Ir associated antigens. Summary of the Proceedings of a Workshop on Ia Antigens Held Nov. 21 and 22, 1974, at the National Institutes of Health, Bethesda, Maryland. Immunogenetics 2, 301, 1975.